Department of Critical Care Medicine, Affiliated Haian Hospital of Nantong University, No. 17 Zhongba Middle Road, Haian, Nantong, 226600, Jiangsu, China.
Department of Medical Imaging, Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nantong, Jiangsu, China.
Sci Rep. 2024 Jul 15;14(1):16317. doi: 10.1038/s41598-024-67444-5.
To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O (PaO), partial pressure of CO (PaCO), partial pressure of O/fraction of inspired O (PaO/FiO) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO, PaCO and PaO/FiO in the model group were significantly reduced (P < 0.01), and PaO, PaCO and PaO/FiO were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation.
研究半胱天冬酶抑制剂对急性呼吸窘迫综合征（ARDS）模型大鼠血流动力学和炎症因子的影响。
将 60 只健康雄性 Wistar 大鼠随机分为三组，即对照组、ARDS 组和 ARDS+Caspase 抑制剂组，每组 20 只。对照组大鼠腹腔内注射 2 mL/kg 生理盐水，ARDS 模型组大鼠腹腔内注射 4 mg/kg 脂多糖（LPS）建立 ARDS 模型，ARDS+Caspase 抑制剂组大鼠在 LPS 注射后腹腔内给予 20 mg/kg Caspase 抑制剂。记录给药前 6、12 h 及给药后各时间点的肺动脉压（PAP）和平均动脉压（MAP）变化。此外，用血气分析仪评估动脉血气，并评估氧分压（PaO）、二氧化碳分压（PaCO）、吸入氧分数的氧分压（PaO/FiO）的变化。另外，测定肺湿/干重（W/D）比和肺组织中炎症因子水平。最后，用病理切片法测定肺动脉中膜厚度（MT）、MT 百分比（MT%）和肌血管化程度。测定大鼠的肺动脉压。
与对照组比较，模型组各时间点肺动脉压均明显升高（P<0.01），MAP 于 6 h 时明显升高（P<0.05）；与模型组比较，给药组大鼠各时间点肺动脉压均明显降低（P<0.01），MAP 于 6 h 时明显降低（P<0.05）。动脉血气分析显示，与对照组比较，模型组 PaO、PaCO 和 PaO/FiO 明显降低（P<0.01），Caspase 抑制剂治疗后 PaO、PaCO 和 PaO/FiO 明显升高（P<0.05 或 0.01）。模型组肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症介质水平明显高于对照组（P<0.01），Caspase 抑制剂治疗后明显降低（P<0.01）。模型组肺动脉 MT、MT%和肌血管化程度明显升高（P<0.05 或 0.01），Caspase 抑制剂治疗后肺动脉 MT 和肌血管化程度明显降低（P<0.05 或 0.01）。含半胱天冬酶募集域的凋亡抑制因子（ARC）通过影响血流动力学和减轻炎症来减轻肺动脉高压（PH）的发生和发展。
